Decreased smooth muscle cells and fibrous thickening of the tunica media in peripheral pulmonary artery stenosis in Alagille syndrome.

Alagille syndrome is caused by mutations in genes involved in NOTCH signaling, specifically JAG1 and NOTCH2, and is associated with a high rate of peripheral pulmonary artery stenosis. In this study, we report the case of an infant with Alagille syndrome caused by a JAG1 mutation, who succumbed to acute exacerbation of right heart failure due to severe peripheral pulmonary artery stenosis. The autopsy revealed that the peripheral pulmonary arteries were significantly stenosed, exhibiting hypoplasia and thickened vessel walls. Histological examination of the pulmonary artery walls showed a decrease in smooth muscle cells in the tunica media and an increase in collagen and elastic fibers, although the intrapulmonary arteries were intact. These findings are important for understanding the pathogenesis of Alagille syndrome and developing treatment strategies for peripheral pulmonary artery stenosis.

Prediction of adverse cardiovascular events in children using artificial intelligence-based electrocardiogram.

BACKGROUND: Convolutional neural networks (CNNs) have emerged as a novel method for evaluating heart failure (HF) in adult electrocardiograms (ECGs). However, such CNNs are not applicable to pediatric HF, where abnormal anatomy of congenital heart defects plays an important role. ECG-based CNNs reflecting neurohormonal activation (NHA) may be a useful marker of pediatric HF. This study aimed to develop and validate an ECG-derived marker of pediatric HF that reflects the risk of future cardiovascular events. METHODS: Based on 21,378 ECGs from 8324 children, a CNN was trained using B-type natriuretic peptide (BNP) and the occurrence of major adverse cardiovascular events (MACEs). The output of the model, or the electrical heart failure indicator (EHFI), was compared with the BNP regarding its ability to predict MACEs in 813 ECGs from 295 children. RESULTS: EHFI achieved a better area under the curve than BNP in predicting MACEs within 180 days (0.826 versus 0.691, p = 0.03). On Cox univariable analyses, both EHFI and BNP were significantly associated with MACE (log10 EHFI: hazard ratio [HR] = 16.5, p < 0.005 and log10 BNP: HR = 4.4, p < 0.005). The time-dependent average precisions of EHFI in predicting MACEs were 32.4%-67.9% and 1.6-7.5-fold higher than those of BNP in the early period. Additionally, the MACE rate increased monotonically with EHFI, whereas the rate peaked at approximately 100 pg/mL of BNP and decreased in the higher range. CONCLUSIONS: ECG-derived CNN is a novel marker of HF with different prognostic potential from BNP. CNN-based ECG analysis may provide a new guide for assessing pediatric HF.

Hemodynamic simulation of complete transposition of the great arteries for optimal treatment strategies based on its circulatory physiology.

Our study aimed to elucidate the role of different shunts and provide novel insights into optimal treatment approaches for complete transposition of the great arteries (TGA), which is characterized by unique and complicated circulatory dynamics. We constructed a computational cardiovascular TGA model and manipulated cardiovascular parameters, such as atrial septal defect (ASD) and patent ductus arteriosus (PDA) sizes, to quantify their effects on oxygenation and hemodynamics. In addition, ASD flow patterns were investigated as innovative indications for balloon atrial septostomy (BAS). Our model of TGA with an intact ventricular septum (TGA-IVS) showed that a large ASD can achieve sufficient mixing for survival without PDA, and the presence of PDA is detrimental to oxygen delivery. A treatment strategy for TGA-IVS that enlarges the ASD as much as possible by BAS and PDA closure would be desirable. In TGA with a ventricular septal defect (TGA-VSD), the VSD allows for higher oxygenation and reduces the detrimental effects of PDA on systemic circulation. In TGA-VSD, both strategies of enlarging the ASD by BAS with a closed PDA and adjusting the PDA in response to pulmonary vascular resistance (PVR) reduction without BAS may be effective. The simulated ASD flow patterns showed that the sharp peak left-to-right flow pattern in systole (σ-wave) reflected the hemodynamically significant ASD size, independent of PDA, VSD, and PVR. The ASD flow pattern visualized by Doppler echocardiography provides clinical insights into the significance of an ASD and indications for BAS, which are not readily apparent through morphological assessment.NEW & NOTEWORTHY Complete transposition of the great arteries (TGA) represents complex and unique circulation that is dependent on blood mixing through multiple interacting shunts. Consequently, the role of each shunt and the treatment strategy remain unclear. We developed a mathematical model of TGA circulation, revealing the significant influence of atrial septal defect (ASD) on oxygenation and hemodynamics. The blood flow pattern through the ASD reflects its hemodynamic impact and helps determine treatment strategies.

Successful use of ivabradine in a 10-year-old patient with graft failure after heart transplantation.

We encountered a paediatric case of graft failure due to antibody-mediated rejection after heart transplantation in which ivabradine was effective. Inappropriate sinus tachycardia in denervated transplanted hearts is a good indication for ivabradine administration as beta-blockers have a limited efficacy. To our knowledge, this is the first report on the effectiveness of ivabradine in a paediatric heart transplant rejection case.

Poor Myocardial Compaction in a Patient with Recessive MYL2 Myopathy.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.